Understanding Ejection Fraction and Heart Failure
Ejection fraction is a measurement, expressed as a percentage, of how much blood the left ventricle pumps out with each contraction. In a healthy heart, this is typically between 50% and 75%. When ejection fraction is reduced, usually below 40%, it is known as heart failure with reduced ejection fraction (HFrEF). This means the heart muscle is weakened and cannot pump blood effectively to the rest of the body.
Guideline-directed medical therapy (GDMT) for HFrEF often involves a combination of medications that work together to improve heart function, reduce symptoms, and prolong life. While no single "magic bullet" tablet exists, several classes of oral medications have been proven to increase ejection fraction over time and improve patient outcomes.
Angiotensin Receptor-Neprilysin Inhibitors (ARNIs)
One of the most significant recent advances in heart failure treatment is the development of Angiotensin Receptor-Neprilysin Inhibitors (ARNIs), with sacubitril/valsartan (brand name Entresto) being the primary example. This medication combines two agents: a neprilysin inhibitor (sacubitril) and an angiotensin II receptor blocker (valsartan).
How ARNIs work
- Sacubitril: Blocks the neprilysin enzyme, preventing it from breaking down natriuretic peptides. These peptides help relax blood vessels, excrete sodium, and reduce the heart's workload.
- Valsartan: Acts like a standard ARB, blocking angiotensin II receptors to further relax blood vessels and lower blood pressure.
The PROVE-HF trial, for example, showed that sacubitril/valsartan significantly improved left ventricular ejection fraction in patients with HFrEF over a period of 6 to 12 months. It has also been shown to reduce hospitalizations and cardiovascular-related death.
Beta-Blockers
Certain beta-blockers are foundational in the treatment of HFrEF and can progressively increase ejection fraction by shielding the heart from damaging stress hormones like adrenaline. They work by slowing the heart rate and reducing blood pressure, which reduces the heart's workload and allows it to function more efficiently over time. The specific beta-blockers proven to be effective for this purpose include:
- Carvedilol (Coreg)
- Metoprolol succinate (Toprol XL)
- Bisoprolol (Zebeta)
SGLT2 Inhibitors
Originally developed for treating type 2 diabetes, SGLT2 inhibitors have been proven to have powerful benefits for heart failure patients, including improved ejection fraction. Medications such as dapagliflozin (Farxiga) and empagliflozin (Jardiance) are now a standard part of GDMT for many patients with HFrEF, regardless of whether they have diabetes. These medications work by promoting the excretion of glucose and sodium through the urine, which reduces the strain on the heart.
Other Important Medications
ACE Inhibitors and ARBs
Angiotensin-converting enzyme (ACE) inhibitors (e.g., lisinopril, enalapril) and angiotensin II receptor blockers (ARBs) (e.g., valsartan, candesartan) help widen blood vessels, which lowers blood pressure and reduces strain on the heart. These medications have been mainstays of HFrEF treatment for years and can help improve ejection fraction. A patient will typically be prescribed either an ACE inhibitor or an ARB, but not both. In many cases, ARNIs are now the preferred option, often replacing a patient's existing ACE inhibitor or ARB.
Mineralocorticoid Receptor Antagonists (MRAs)
MRAs, such as spironolactone (Aldactone) and eplerenone (Inspra), are often added to a patient's medication regimen to provide additional benefits. They help to regulate fluid and salt balance and provide a protective effect on the heart muscle.
Digoxin
Digoxin is an older medication that works as a positive inotrope, meaning it increases the strength of the heart's contractions. It is not a first-line therapy for increasing ejection fraction but may be used to help manage symptoms and reduce hospitalizations in patients with severe HFrEF who remain symptomatic despite taking other guideline-directed medications.
Comparison of key heart failure medications
| Medication Class | Example Tablets | Mechanism of Action | Effect on Ejection Fraction | Use Case |
|---|---|---|---|---|
| ARNIs | Sacubitril/Valsartan (Entresto) | Blocks neprilysin and angiotensin II receptors to relax blood vessels and reduce heart strain. | Significant increase over time. | First-line therapy for many HFrEF patients. |
| Beta-Blockers | Carvedilol, Metoprolol Succinate, Bisoprolol | Slows heart rate and blood pressure; blocks stress hormones. | Progressive improvement over time. | Core component of GDMT for HFrEF. |
| SGLT2 Inhibitors | Dapagliflozin (Farxiga), Empagliflozin (Jardiance) | Promotes excretion of glucose and sodium, reducing cardiac workload. | Shown to improve heart function and reduce hospitalizations. | Added to other HFrEF medications. |
| ACE Inhibitors | Lisinopril, Enalapril | Widens blood vessels, lowering blood pressure and heart strain. | Improves over time, especially when combined with other drugs. | Often replaced by ARNIs in appropriate patients. |
| Digoxin | Digoxin (Lanoxin) | Increases the strength of heart muscle contractions. | Can increase ejection fraction, but primarily used for symptomatic relief. | Added for patients with severe symptoms on other therapies. |
Conclusion
While a single pill will not cure heart failure, a combination of medications has been shown to improve ejection fraction and overall heart health for patients with HFrEF. The cornerstone of this treatment is guideline-directed medical therapy (GDMT), which may include modern drugs like sacubitril/valsartan and SGLT2 inhibitors alongside established therapies like beta-blockers. The specific regimen is tailored to each individual, based on their symptoms, medical history, and tolerability of medications. It is essential for patients to work closely with their healthcare team to find the right combination of tablets and adhere to the prescribed plan to achieve the best possible outcomes. For further information, the American Heart Association provides extensive resources on heart failure management.(https://www.heart.org/en/health-topics/heart-failure/treatment-options-for-heart-failure/medications-used-to-treat-heart-failure).
